This review summarizes the data on the functioning of carriers providing electroneutral symport of sodium, potassium, and chloride (Na(+),K(+),2Cl(-) cotransport), potassium and chloride (K(+),Cl(-) cotransport), and sodium and chloride (K(+),Cl(-) cotransport) as well as molecular mechanisms of the regulation of these carriers and their physiological significance. We emphasized the involvement of chloride-coupled carriers in the regulation of cell volume and intracellular chloride concentration and novel data on the role of ubiquitous isoform of Na(+),K(+),2Cl(-) cotransporter NKCC1 in regulation of vascular smooth muscle contraction and activity of GABA(A) receptors. Finally, we analyzed the data on activation of NKCC1 in patients with essential hypertension and its role in the long-term maintenance of elevated systemic blood pressure and myogenic response in microcirculatory beds.